Fixation stability and scotoma mapping for patients with low vision.

PURPOSE: To develop a simplified device that performs fundus perimetry techniques such as fixation mapping and kinetic perimetry. METHODS: We added visual stimulation to a near-infrared retinal imager, the laser scanning digital camera (LSDC). This device uses slit scanning illumination combined with a two-dimensional CMOS (complementary metal oxide semiconductor) detector, with continuous viewing of the retina. The CMOS readout was synchronized with the slit scanning, thereby serving as a confocal aperture to reduce stray light in retinal images. A series of retinal images of 36 degrees was automatically aligned to provide data for fixation maps and quantification of fixation stability. The LSDC and alignment techniques also provided fundus viewing with retinal location correction for scotoma mapping. RESULTS: First, fixation mapping was readily performed in patients with central scotoma or amblyopia. The automatic alignment algorithm allowed quantification of fixation stability in patients with macular pathologies that did not cause scotoma. Second, fixation stability was rapidly and quantitatively assessed by the automatic registration of the series of retina images. There was no significant difference in the fixation stability with automatic versus manual alignment. Kinetic perimetry demonstrated that fundus imaging helped reduce the variability of perimetric data by identifying and preventing false-positives caused by eye motion. We found that the size of the blind spot was significantly larger for dark targets on brighter backgrounds than when the contrast was reversed (p < 0.045). This is consistent with incremental targets being detected partially or wholly because of scattered light falling on more sensitive retinal locations. CONCLUSIONS: Fundus perimetry with the LSDC allows for a wide range of fixation and perimetry tasks.

Local flicker stimulation evokes local retinal blood velocity changes.

We investigated the effect of localized visual stimulation on human retinal blood velocity using an adaptive optics scanning laser ophthalmoscope (AOSLO). To measure the blood velocity response, the AOSLO scanning raster was moved over the target arteries and red blood cell velocity was measured. Localized visual stimuli were delivered by projecting flicker patterns inside or outside the target artery's downstream region. The blood velocity increased in the presence of a flicker stimulus in the downstream region but not when outside the downstream region. The blood velocity increased more with larger area of stimulation. This increase was significant even when the stimulus was smaller than 600 µm × 600 µm. These findings suggest that when the retina regulates its blood flow to metabolic demands, it regulates blood velocity in the vascular system selectively, according to activity of neurons within its field of influence.

Noninvasive measurements and analysis of blood velocity profiles in human retinal vessels.

PURPOSE: To quantitatively model the changes in blood velocity profiles for different cardiac phases in human retinal vessels. METHODS: An adaptive optics scanning laser ophthalmoscope (AOSLO) was used to measure blood velocity profiles in three healthy subjects. Blood velocity was measured by tracking erythrocytes moving across a scanning line. From the radial position of the cells within the lumen, the blood velocity profile was computed. The cardiac pulsatility was recorded with a cardiac signal monitor. RESULTS: The shape of the blood velocity profile in retinal arteries changed systematically during the cardiac cycle, with the flattest profile occurring during the diastolic phase. The measured blood velocity profiles were typically flatter than the commonly assumed parabolic shape. The flatness increased with decreasing vessel size. For the large veins (>80 µm), the ratio of the centerline velocity to the cross-sectional average velocity was between 1.50 and 1.65. This ratio decreased to 1.36 in the smallest vein studied (32 µm). Velocity profiles downstream from a venous confluence showed two peaks at 120 µm from the confluence, but a single velocity peak 500 µm downstream from the confluence. CONCLUSIONS: The cardiac cycle influences the blood flow velocity profiles systematically in retinal arteries but not in veins. Parabolic flow was not found in even the largest vessels studied, and deviations from parabolic flow increased in smaller vessels. The measurements are sensitive enough to measure the dual-humped blood velocity profile at a vein confluence.

Delayed appearance of high altitude retinal hemorrhages.

BACKGROUND: Retinal hemorrhages have been described as a component of high altitude retinopathy (HAR) in association with altitude illness. In this prospective high altitude study, we aimed to gain new insights into the pathophysiology of HAR and explored whether HAR could be a valid early indicator of altitude illness. METHODOLOGY/PRINCIPAL FINDINGS: 28 mountaineers were randomly assigned to two ascent profiles during a research expedition to Mt. Muztagh Ata (7546 m/24,751 ft). Digital fundus photographs were taken prior to expedition at 490 m (1,607 ft), during expedition at 4497 m (14,750 ft = base camp), 5533 m (18,148 ft), 6265 m (20,549 ft), 6865 m (22,517 ft) and 4.5 months thereafter at 490 m. Number, size and time of occurrence of hemorrhages were recorded. Oxygen saturation (SpO2) and hematocrit were also assessed. 79% of all climbers exhibited retinal hemorrhages during the expedition. Number and area of retinal bleeding increased moderately to medium altitudes (6265 m). Most retinal hemorrhages were detected after return to base camp from a high altitude. No post-expeditional ophthalmic sequelae were detected. Significant negative (SpO2 Beta: -0.4, p<0.001) and positive (hematocrit Beta: 0.2, p = 0.002, time at altitude Beta: 0.33, p = 0.003) correlations with hemorrhages were found. CONCLUSIONS/SIGNIFICANCE: When closely examined, a very large amount of climbers exhibit retinal hemorrhages during exposure to high altitudes. The incidence of retinal hemorrhages may be greater than previously appreciated as a definite time lag was observed between highest altitude reached and development of retinal bleeding. Retinal hemorrhages should not be considered warning signs of impending severe altitude illness due to their delayed appearance.

New insights into changes in corneal thickness in healthy mountaineers during a very-high-altitude climb to Mount Muztagh Ata.

OBJECTIVE: To investigate the effect of very high altitude and different ascent profiles on central corneal thickness (CCT). METHODS: Twenty-eight healthy mountaineers were randomly assigned to 2 different ascent profiles during a medical research expedition to Mount Muztagh Ata (7546 m) in western China. Group 1 was allotted a shorter acclimatization time prior to ascent to 6265 m. The main outcome measure was CCT. Secondary outcome measures were oxygen saturation (SpO(2)) and symptom assessments of acute mountain sickness (cerebral acute mountain sickness score). Examinations were performed at 490, 4497, 5533, and 6265 m. RESULTS: Central corneal thickness increased in both groups with increasing altitude and decreased after descent. In group 1 (with the shorter acclimatization), mean CCT increased from 537 to 572 microm. Mean CCT in group 2 increased from 534 to 563 microm (P = .048). The amount of decrease in SpO(2) paralleled the increase in CCT. There was no significant decrease in visual acuity. There was a significant correlation between CCT and cerebral acute mountain sickness score when controlled for SpO(2) and age. CONCLUSIONS: Corneal swelling during high-altitude climbs is promoted by low SpO(2). Systemic delivery of oxygen to the anterior chamber seems to play a greater role in corneal oxygenation than previously thought. Adhering to a slower ascent profile results in less corneal edema. Visual acuity in healthy corneas is not adversely affected by edema at altitudes of up to 6300 m. Individuals with more acute mountain sickness-related symptoms had thicker corneas, possibly due to their higher overall susceptibility to hypoxia.

Intraocular pressure during a very high altitude climb.

PURPOSE: Reports on intraocular pressure (IOP) changes at high altitudes have provided inconsistent and even conflicting RESULTS: The purpose of this study was to investigate the effect of very high altitude and different ascent profiles on IOP in relation to simultaneously occurring ophthalmic and systemic changes in a prospective study. METHODS: This prospective study involved 25 healthy mountaineers who were randomly assigned to two different ascent profiles during a medical research expedition to Mt. Muztagh Ata (7,546 m/24,751 ft). Group 1 was allotted a shorter acclimatization time before ascent than was group 2. Besides IOP, oxygen saturation (SaO(2)), acute mountain sickness symptoms (AMS-c score), and optic disc appearance were assessed. Examinations were performed at 490 m/1,607 ft, 4,497 m/14,750 ft, 5,533 m/18,148 ft, and 6,265 m/20,549 ft above sea level. RESULTS: Intraocular pressure in both groups showed small but statistically significant changes: an increase during ascent from 490 m/1,607 ft to 5,533 m/18,148 ft and then a continuous decrease during further ascent to 6,265 m/20,549 ft and on descent to 4,497 m/14,750 ft and to 490 m. Differences between groups were not significant. Multiple regression analysis (IOP-dependent variable) revealed a significant partial correlation coefficient of beta = -0.25 (P = 0.01) for SaO(2) and beta = -0.23 (P = 0.02) for acclimatization time. DISCUSSION: Hypobaric hypoxia at very high altitude leads to small but statistically significant changes in IOP that are modulated by systemic oxygen saturation. Climbs to very high altitudes seem to be safe with regard to intraocular pressure changes.

Ocular blood flow assessment using continuous laser Doppler flowmetry.

This article describes the technique of continuous laser Doppler flowmetry (LDF) as applied to the measurement of the flux of red blood cells in the optic nerve head, iris and subfoveal choroid. Starting with the exposition of the physical principles underlying LDF, we first describe the various devices developed to perform LDF in these vascular beds. We then discuss the clinical protocols, blood flow parameters, calibration procedures, reproducibility and limitations of the LDF technique. Various problems still need to be solved in order to bring to light the full potential of LDF in the assessment of microcirculatory haemodynamics.

New insights into ocular blood flow at very high altitudes.

Little is known about the ocular and cerebral blood flow during exposure to increasingly hypoxic conditions at high altitudes. There is evidence that an increase in cerebral blood flow resulting from altered autoregulation constitutes a risk factor for acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) by leading to capillary overperfusion and vasogenic cerebral edema. The retina represents the only part of the central nervous system where capillary blood flow is visible and can be measured by noninvasive means. In this study we aimed to gain insights into retinal and choroidal autoregulatory properties during hypoxia and to correlate circulatory changes to symptoms of AMS and clinical signs of HACE. This observational study was performed within the scope of a high-altitude medical research expedition to Mount Muztagh Ata (7,546 m). Twenty seven participants underwent general and ophthalmic examinations up to a maximal height of 6,800 m. Examinations included fundus photography and measurements of retinal and choroidal blood flow, as well as measurement of arterial oxygen saturation and hematocrit. The initial increase in retinal blood velocity was followed by a decrease despite further ascent, whereas choroidal flow increase occurred later, at even higher altitudes. The sum of all adaptational mechanisms resulted in a stable oxygen delivery to the retina and the choroid. Parameters reflecting the retinal circulation and optic disc swelling correlated well with the occurrence of AMS-related symptoms. We demonstrate that sojourns at high altitudes trigger distinct behavior of retinal and choroidal blood flow. Increase in retinal but not in choroidal blood flow correlated with the occurrence of AMS-related symptoms.

In vivo measurement of erythrocyte velocity and retinal blood flow using adaptive optics scanning laser ophthalmoscopy.

In vivo measurement of retinal blood flow is obtained by measuring the blood velocity of erythrocytes and lumen diameters of the blood vessels using an adaptive optics scanning laser ophthalmoscope. Erythrocyte velocity is measured by tracking erythrocytes moving across a horizontal scanning line. This approach provides high temporal bandwidth measurements, allowing the fluctuation of blood flow during cardiac cycles to be measured. The technique is most applicable to medium-sized blood vessels.

Regulation of subfoveal choroidal blood flow in age-related macular degeneration.

PURPOSE: To assess the capability of the subfoveal choroidal circulation to regulate its blood flow in response to an acute increase in ocular perfusion pressure in the eyes of healthy elderly persons or of subjects with neovascular age-related macular degeneration (AMD). METHODS: Changes of subfoveal choroidal blood velocity (ChBVel), volume (ChBVol), and flow (ChBF) induced by isometric exercise were determined using laser Doppler flowmetry (LDF) in 19 young healthy volunteers (group 1), 24 elderly healthy volunteers with mild macular pigment distribution changes (group 2), and 23 subjects with subfoveal classic neovascularization caused by AMD (group 3). RESULTS: Isometric exercise induced significant increases in mean ocular perfusion pressure (PPm) of 19.5% +/- 4.9%, 20.2% +/- 3.8%, and 23.2% +/- 4.2%, for groups 1, 2, and 3, respectively (mean +/- 95% confidence interval). In groups 1 and 2, the increase in PPm did not induce significant changes in the mean values of the different LDF parameters. In group 3, however, ChBF increased significantly by 12.4% +/- 5.0%. No significant correlations were found between age and the changes of each of the LDF parameters and of PPm at the end of squatting for the young and elderly healthy groups. CONCLUSIONS: In response to an acute, moderate increase in PPm induced by isometric exercise, subfoveal choroidal blood flow behaves similarly in young and elderly healthy persons and is not significantly different from its value at rest. In contrast, in patients with neovascular AMD, this flow increases, indicating altered regulation in response to the increase in PPm.

Ray tracing model for the estimation of power spectral properties in laser Doppler velocimetry of retinal vessels and its potential application to retinal vessel oximetry.

A new model based on ray tracing was developed to estimate power spectral properties in laser Doppler velocimetry of retinal vessels and to predict the effects of laser beam size and eccentricity as well as absorption of laser light by oxygenated and reduced hemoglobin. We describe the model and show that it correctly converges to the traditional rectangular shape of the Doppler shift power spectrum, given the same assumptions, and that reduced beam size and eccentric alignment cause marked alterations in this shape. The changes in the detected total power of the Doppler-shifted light due to light scattering and absorption by blood can also be quantified with this model and may be used to determine the oxygen saturation in retinal arteries and veins. The potential of this approach is that it uses direct measurements of Doppler signals originating from moving red blood cells. This may open new avenues for retinal vessel oximetry.

Choroidal blood flow during exercise-induced changes in the ocular perfusion pressure.

PURPOSE: The high metabolic rate of the human retina is supported by the choroidal vasculature. Knowledge of the normal choroidal blood flow (ChBF) responses to various physiological stimuli is therefore highly important if the pathophysiology of ocular diseases involving the choroid is to be understood better. In the present study, the hemodynamic responses of the subfoveal ChBF were examined during and after an exercise-induced increase in the ocular perfusion pressure (OPP). METHODS: Twenty-six healthy volunteers, 19 to 55 years of age participated in this two-phase study. Each subject increased resting OPP through stationary biking at a heart rate (HR) of 140 beats per minute (bpm) over 20 minutes. The ChBF was measured by laser Doppler flowmetry (LDF), the systemic BP by electronic sphygmomanometry, and the resting intraocular pressure (IOP) by applanation tonometry. RESULTS: The OPP increased by approximately 43% at the onset of biking, and then decreased biphasically to approximately 12% above resting value by the end of biking. The ChBF remained within 10% of its basal value throughout biking. Immediately after biking, the OPP decreased twice as much as the ChBF in the same time frame. CONCLUSIONS: The dissociation between the OPP and the ChBF during biking and recovery suggests that some mechanism keeps the ChBF close to its basal value, an observation that indicates blood flow regulation.

Blood pO2 and blood flow at the optic disc.

A fundus camera-based phosphorometer to noninvasively and quasicontinuously measure the blood partial pressure of oxygen (pO(2,blood)) in the microvasculature of the pig optic nerve using the principle of the phosphorescence quenching by O(2) is described. A porphyrin dye is injected into the venous circulation and the decay of its phosphorescence emission is detected locally in the eye, after excitation with a flash of light. Combined with blood flow measurements by means of a laser Doppler flowmeter mounted on the phosphorometer, we demonstrate the capability of the instrument to determine the time course of optic nerve blood flow and pO(2,blood) in response to various physiological stimuli, such as hyperoxia and hypercapnia. This instrument appears to be a useful tool for the investigation of the oxygenation of the optic nerve.

Feasibility of LDF measurements of optic nerve head blood flow in children with cerebral malaria.

The pathogenesis of cerebral malaria (CM), a significant cause of death in the tropics, is still not understood. Cerebral blood flow measurements would be important but are difficult under the conditions prevailing in CM clinics in the tropics. With the goal of using optic nerve head (ONH) blood flow (F(onh)) instead of cerebral blood flow to help outcome prediction, we have tested the feasibility of performing F(onh) measurements in comatose CM children, using a portable ocular laser Doppler flowmeter (LDF). Measurements were performed in one eye of each of 13 children (2.7 +/- 1.1 years) during a period of about 8 min. The Vel(onh) (the relative blood velocity), Vol(onh) (the relative blood volume), and F(onh) values were determined for each child from three to five measurements of 2 to 20 s. Average Vel(onh), Vol(onh), and F(onh) values were 0.49 +/- 0.08 kHz, 2.4 +/- 1.06 arbitrary units (a.u.), and 89 +/- 16.8 a.u., respectively. The average coefficients of variation of the flow parameters based on all segments in each child were 13 +/- 9% (range 1-29%) for Vel(onh), 27 +/- 13% (range 3-65%) for Vol(onh), and 23 +/- 12% (range 5-42%) for F(onh). This study demonstrates the feasibility of LDF measurements in CM children. The large range of these coefficients of variations could be due to the presence of fluctuations of ONH blood flow on a short time scale in these neurologically unstable children.

Effect of isovolumic hemodilution on oxygen delivery to the optic nerve head.

BACKGROUND: To investigate the effect of isovolumic hemodilution on the tissue oxygenation of the optic nerve head (ONH). MATERIAL AND METHODS: In 9 miniature pigs (6 - 12 kg), hemodilution was performed by replacing 100 - 140 ml of blood by an equivalent volume of 6 % hydroxyethyl starch in saline. The blood flow parameters in the ONH microcirculation, namely velocity (BVel), volume (BVol) and flow (BF), were measured by laser Doppler flowmetry. Microelectrodes placed at approximately 50 micrometer from the disk surface and the phosphorescence quenching technique were used to measure pO 2 in the vitreous (pO 2 (vitr)) and in the ONH capillary blood (pO 2 (blood)), respectively. Arterial blood pressure, hematocrit (Hct) and gas content were documented. RESULTS: In all animals, hemodilution reduced Hct by 30 +/- 6 %. All the flow parameters increased markedly. Simultaneously, pO 2 (blood) (baseline: 31 +/- 3 mm Hg) dropped to approximately 75 % of its initial value, while pO 2 (vitr) (baseline: 26 +/- 8 mm Hg) increased by 15 +/- 8 %. CONCLUSIONS: Hemodilution leads to an increase of pO 2 (vitr) reflecting a similar rise of the ONH tissue pO 2. This effect results from an enhanced blood perfusion of the ONH, which over-compensates the decrease of the blood O 2 content.